Present information implicates virus-associated host autoreactive responses in the development of a number of acute and chronic neuroologic disorders of the CNS of humans which would appear to have an immunopathogenetic basis, e.g., post-measles disseminated encephalomyelitis and multiple sclerosis, represented by all of its subacute-chronic remitting and progressive variant forms. Virus mutants or strains with a propensity for establishing cell-associated, persistent CNS infections would appear to be of central importance in initiating the immunohistopathologic features of these neurologic disorders. An exceptionally promising hamster model disease system. Characterized by persistent CNS infection due to the HBS mutantstrain of measles virus which results in striking augmentation of experimental allergic encephalomyelitis (EAE) induced by sensitization to neural antigen, will be studied to definitively clarify two pressing issues: (1) Whether antigenic determinants of the persistent HBS virus or "neo-neural antigen(s)" resulting from the persistent infection vis-a-vis native CNS antigenic constituents are or are not essential components of the CNS target tissue. (2) Whether the persistent HBS virus infection does or does not exert an immunomodulating influence on host responses to injected CNS tissue or defined/purified neural antigenic constituents, such as myelin basic protein or cerebroside-galactocerebroside, causing enhancement of neuroautoimmune responses directed against the CNS of the infected-sensitized host. In addition, preliminary data suggesting that persistent HBS infection of the CNS causes subtle abnormalities in the non-EAE inducing regions of the myelin basic protein molecule will be pursued using tryptic peptide mapping. Alterations in cerebrovascular permeability resulting from the CNS virus infection will be studied using 125I/T31 I double labels and horse radish peroxidase coupled electron microscopy.